Ejection fraction (EF) is defined as the ratio of the stroke volume (SV) to the ventricular end-diastolic volume (EDV) and is expressed in percent. More simply, EF represents the percentage of the total volume in a ventricular chamber that is ejected per beat. EF is perhaps the most clinically significant index of global ventricular function. For example, epidemiological data have shown a powerful curvilinear relationship between left ventricular (LV) EF and outcome in patients with heart failure. As another example, a reduced LVEF has recently been recommended as the single factor for determining which post-myocardial infarction (heart attack) patients should be implanted with a potentially life-saving, but expensive, defibrillator. Thus, methods and apparatus for effectively monitoring EF are extremely desirable in that they would greatly facilitate the monitoring, diagnosis, and treatment of cardiovascular disease.
Several methods have been developed for measuring EF or ventricular volume. Note that EF may be trivially computed from the ventricular EDV and end-systolic volume (ESV) as follows:
                              E          ⁢                                          ⁢          F                =                                            S              ⁢                                                          ⁢              V                                      E              ⁢                                                          ⁢              D              ⁢                                                          ⁢              V                                =                                                                      E                  ⁢                                                                          ⁢                  D                  ⁢                                                                          ⁢                  V                                -                                  E                  ⁢                                                                          ⁢                  S                  ⁢                                                                          ⁢                  V                                                            E                ⁢                                                                  ⁢                D                ⁢                                                                  ⁢                V                                      .                                              (        1        )            In clinical practice, EF is primarily determined by imaging the ventricular volume via echocardiography (transthoracic or transesophageal), radionuclide techniques (first pass or equilibrium), contrast angiography, ultra-fast computed tomography (CT), and magnetic resonance imaging (MRI). Each of these imaging methods offers some advantages and disadvantages with respect to each other in terms of, for example, the level of invasiveness, need for radiation exposure or contrast agents, and assumptions about ventricular geometry. However, imaging methods generally suffer from the major disadvantages of requiring an expert operator as well as bulky and expensive equipment. Thus, EF measurements can only be obtained in the clinical setting and are usually made few and far between (e.g., days to months).
To improve upon the significant disadvantages shared by imaging techniques, a few methods have been introduced for continuous and automatic monitoring of EF or ventricular volume. These methods include continuous thermodilution technique, the non-imaging nuclear monitor, the conductance catheter, and sonomicrometry. However, these methods are all limited in at least one clinically significant way.
The continuous thermodilution method involves automatic heating of blood in the right ventricle via a thermal filament, measurement of the temperature changes downstream in the pulmonary artery via a fast response thermistor, construction of a bolus thermodilution washout decay curve, and estimation of right ventricular (RV) EF based on the extent of the temperature decay over a cardiac cycle. An attractive feature of this method is that it requires only a pulmonary artery catheterization, which is routinely performed in a subset of critically ill patients (see below). As a result, the method is sometimes conducted in clinical practice, though it has yet to gain widespread popularity. On the other hand, the method does not provide beat-to-beat estimates of RVEF but rather estimates at time intervals of approximately a minute or more. Furthermore, the method continually perturbs the circulation and is not amenable to ambulatory or home health care monitoring, both of which could potentially reduce hospital admissions and health care costs. But, perhaps the most significant limitation of this method is that it cannot be utilized to determine the more clinically relevant LVEF.
In contrast, the non-imaging nuclear monitor, the conductance catheter, and sonomicrometry do permit automatic, beat-to-beat monitoring of LVEF. However, as discussed below, the substantial limitations of each of these methods have precluded their use in clinical practice.
In non-imaging nuclear monitoring of LVEF, the patient is given an injection of a radioactive tracer, which distributes throughout the circulation. The amount of the radioactive tracer in the LV is then measured with a crystal scintillation detector attached to a single bore converging collimator. The method is able to monitor LV volume at a high temporal resolution (10 ms) by sacrificing the spatial resolution, which would otherwise be needed to produce images. An appealing feature of the method is that LVEF is estimated without any assumptions about ventricular geometry. Additionally, systems have been developed for both bedside and ambulatory monitoring. However, the method is not in clinical use because of the difficulty in positioning the detector at the appropriate location on the patient's chest and in correcting for background radioactivity originating from extra-cardiac regions. The method also has the obvious disadvantage of exposing the patient to radiation.
The conductance catheter method involves placing a multi-electrode catheter in a ventricular cavity, continually applying AC current to the electrodes to generate an electric field, measuring the resulting voltage gradients, and estimating the ventricular volume from the intra-ventricular conductance using geometric assumptions. Thus, the method is able to provide estimates of either LVEF or RVEF. However, for LVEF, the method requires a left heart catheterization, which is rarely performed in critically ill patients. Moreover, the method is not capable of accurately estimating absolute or proportional ventricular volume, which is needed to reliably compute EF, due mainly to the parallel conductance (offset error) and non-uniformity of the generated electric field (scale factor error). Finally, another disadvantage of this method is that it is not amenable to ambulatory or home health care monitoring.
Sonomicrometry involves suturing crystals to opposite sides of the ventricular endocardium and using the ultrasound transit time principle to estimate the ventricular volume based on geometric assumptions. While the method can provide accurate estimates of either LVEF or RVEF when a sufficient number of crystals are used, it is obviously much too invasive to ever be employed in clinical practice.
It would be desirable to be able to accurately monitor beat-to-beat LVEF and beat-to-beat RVEF based on the mathematical analysis of continuous blood pressure. Continuous blood pressure is routinely monitored in clinical practice and several systems are currently available for continuous monitoring of specifically systemic arterial pressure (SAP, e.g., invasive catheters, non-invasive finger-cuff photoplethysmography, non-invasive arterial tonometry, and implanted devices), LV pressure (LVP, e.g., implanted devices), pulmonary artery pressure (PAP, e.g., invasive pulmonary artery catheters and implanted devices), and RVP (e.g., invasive pulmonary artery catheters and implanted devices). Thus, in contrast to the aforementioned methods, this approach would readily permit continuous and automatic measurement of LVEF and RVEF in the context of several important clinical applications. For example, such an approach could be applied to: 1) routinely employed invasive SAP and PAP catheter systems for titrating therapy in the intensive care unit (ICU), continuous monitoring of cardiac surgery in the operating room (OR), and remote ICU monitoring; 2) implanted SAP, PAP, and RVP systems for chronic, ambulatory monitoring of cardiovascular disease and facilitating the diagnosis of ischemia with surface ECGS; and 3) non-invasive SAP systems for emergency room (ER) or home health care monitoring. Note that these clinical applications of continuous and automatic EF monitoring have, for the most part, not been realized with the currently available measurement methods. Moreover, a blood pressure-based approach could estimate EF without making any assumptions about the ventricular geometry.
The statements in this section merely provide background information related to the present disclosure and may not constitute prior art